A New Treatment for HCV Genotype 1b Patients?

Results of a phase III, open-label study that evaluated daclatasvir and asunaprevir in interferon- ineligible and/or intolerant non-Japanese Asian patients with chronic hepatitis C virus (HCV) genotype 1b infection found that the combination led to sustained virologic response at post-treatment week 24 (SVR24) in 91% of patients from China. The rate of SVR24 rose to 98% among those without nonstructural protein 5A (NS5A) resistance-associated variants (RAVs) at baseline.

Presented on February 22 at the Asian Pacific Association for the Study of the Liver Conference (APASL), the study focuses on the genotype that is particularly prevalent in China, where interferon/ribavirin combination regimens are still the current standard of care. For the open-label study, 159 patients received daclatasvir 60 mg (tablet) once daily plus asunaprevir 100 mg (soft capsule) twice daily for 24 weeks. Of these patients, 80% were from mainland China, 11% from Korea, and 9% from Taiwan.

All subgroups with genotype 1b HCV in the study had similarly high rates of SVR24, including those with cirrhosis (90%), patients from Korea (94%), and patients from Taiwan (87%). Overall, patients without baseline NS5A RAVs had an SVR24 rate of (99%), regardless of whether they had cirrhosis, compared with a rate of only 42% in those with baseline NS5A RAVs. These findings suggest that screening for the presence of specific NS5A mutations may help healthcare providers determine which patients would benefit most from treatment and possibly achieve a cure with an NS5A-containing medication regimen.

Across all patient cohorts, all serious adverse events (3%), grade 4 laboratory abnormalities (< 2%), and mortalities (1%) that occurred while on treatment were determined to be unrelated to the study drugs. Only two patients discontinued the study due to adverse events, the most common of which were decrease in platelets (9%), upper respiratory tract infection (8%), alanine aminotransferase increase (7%), absolute neutrophil count decrease (7%), monocyte decrease (6%), white blood cell decrease (6%), thrombocytopenia (6%), and pruritus (6%).

“These results signal that the daclatasvir and asunaprevir regimen could provide a highly effective all-oral, interferon- and ribavirin-free treatment for many Chinese HCV patients with genotype 1b infection,” said Lai Wei, MD, Professor of Hepatology & Medicine; Director of the Peking University Hepatology Institute; and Chief of the Department of Hepatology, at Peking University People’s Hospital. “This is an important finding because the burden of HCV in China is extremely high, and newer direct-acting antivirals have yet to be introduced for any patients.”

Adding to Wei’s sentiments, Douglas Manion, MD, head of Specialty Development at BMS, said “So much progress has been made globally in the fight against chronic hepatitis C, but the battle against the disease is not over. At Bristol-Myers Squibb, we continue to seek out areas and patient populations that remain in need of new treatment solutions, such as China, where at last count 13 million people are estimated to be living with the disease.”